Biological Psychiatry
Volume 56, Issue 4 , Pages 217-224, 15 August 2004

A polymorphism of the β1-adrenergic receptor is associated with low extraversion

  • Murray B. Stein

      Affiliations

    • Department of Psychiatry (MBS, NJS), University of California San Diego, San Diego, California, USA
    • Department of Psychology (MBS), San Diego State University, San Diego, California, USA
  • ,
  • Nicholas J. Schork

      Affiliations

    • Department of Psychiatry (MBS, NJS), University of California San Diego, San Diego, California, USA
  • ,
  • Joel Gelernter

      Affiliations

    • Department of Psychiatry (JG), Yale University School of Medicine, West Haven, Connecticut, USA
    • Corresponding Author InformationAddress reprint requests to Joel Gelernter, M.D., Yale University School of Medicine, VA Psychiatry 116A2, 950 Campbell Avenue, West Haven, CT 06516

Received 13 August 2003; received in revised form 4 May 2004; accepted 27 May 2004.

Background

We examined the possibility that allelic variation leading to alterations in β1-adrenergic function might be present in persons with elevated social anxiety–related traits.

Methods

A sample of 504 undergraduate college students were phenotyped on a personality inventory (the NEO-Personality Inventory-Revised) and measures of shyness and social anxiety and genotyped for two β1 adrenergic (ADRB1 gene) polymorphisms: a serine/glycine substitution at amino acid 49 (Ser49Gly) and an arginine/glycine substitution at residue 389 (Arg389Gly). We hypothesized that the Gly49 variant (thought to be functional), but not variation at Arg389Gly, would be associated with (low) extraversion and shyness. We evaluated the potential for population stratification artifact by genotyping a set of 36 unlinked, highly polymorphic markers previously demonstrated to sufficiently distinguish the ancestry of major American populations.

Results

Presence of a Gly49 allele was associated with an increased odds of having low or very low extraversion (odds ratio = 1.68, 95% confidence interval 1.05–2.71). The Arg389Gly polymorphism, although in tight linkage disequilibrium (D′ = −1.00) with Ser49Gly, was not significantly associated with level of extraversion. Formal testing showed that population structure did not explain the findings.

Conclusions

The Ser49Gly functional polymorphism in the β1 adrenergic receptor might explain some of the population variance in extraversion and related personality traits. Population structure was excluded as an explanation for these findings. We used a sufficient marker set to exclude possible population stratification artifact. These findings should be replicated and extended to the study of psychiatric disorders marked by low extraversion, namely social phobia and other phobic disorders.

Keywords:  Beta adrenergic receptor , extraversion , genetic polymorphism , personality , shyness , social anxiety

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PII: S0006-3223(04)00650-X

doi:10.1016/j.biopsych.2004.05.020

Biological Psychiatry
Volume 56, Issue 4 , Pages 217-224, 15 August 2004